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MS 11089 Received 11 May 2000; accepted after revision 21 June 2000.
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ABSTRACT |
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INTRODUCTION |
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In skeletal muscle of vertebrates, it is generally thought that coordination of contraction is achieved by an action potential passing along the length of the fibre via the surface membrane (sarcolemma), sequentially depolarising the individual transverse tubular (T-) networks associated with successive sarcomeres (Lüttgau & Stephenson, 1986; Horowicz & Spalding, 1994). This leads to the activation of specialised voltage-sensor molecules located in the T-system that in turn activate the Ca2+-release channels in the adjacent sarcoplasmic reticulum (SR), leading to a rise in myoplasmic [Ca2+] and muscle contraction (Melzer et al. 1995). It was originally proposed that the spread of excitation down into the T-system of frog muscle fibres was a passive process (Huxley & Taylor, 1958), though later evidence indicated that it was mediated by action potentials (Costantin, 1970; Bezanilla et al. 1972; Nakajima & Gilai, 1980). This question has not been directly addressed in mammalian muscle fibres, and given the comparatively small diameter of such fibres, it is possible that excitation spreads inwards passively.
Here we use muscle fibres in which the surface membrane has been physically removed (Lamb & Stephenson, 1990, 1994) and show that transverse electrical field stimulation elicits twitch and tetanic force responses comparable to those observed in intact muscle fibres. The properties of these responses show that they are mediated by action potential propagation within the T-system. The results also demonstrate that the normal excitation-contraction (E-C) coupling mechanism is retained and functions well in these skinned fibres. Finally, we report evidence showing that action potentials travel longitudinally inside muscle fibres over long distances, via connections between the T-systems of adjacent sarcomeres. Such conduction probably helps in the coordination of muscle contraction along a fibre, and may be particularly important in reducing the susceptibility of muscle to fatigue involving action potential failure within the T-system, such as during continuous, vigorous contraction (Fitts, 1994; Allen et al. 1995).
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METHODS |
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A skinned fibre preparation was used, as described previously (Lamb & Stephenson, 1990, 1994). Long-Evans rats were anaesthetised with halothane (2 % v/v) and killed by asphyxiation, in accordance with guidelines of the Animal Ethics Committee of La Trobe University. Whole extensor digitorum longus (EDL) muscles were dissected from the rat and bathed in an extracellular solution (mM: NaCl, 145; KCl, 3; CaCl2, 2·5; MgCl2, 1; Hepes, 10; pH 7·4) for 30 min (with or without 10 µM TTX), blotted dry and immersed in paraffin oil. Single fibre segments were mechanically skinned, as shown in Fig. 1A, mounted between fixed forceps and a force transducer (AME875, SensoNor, Horten, Norway), stretched to 120 % of resting length (sarcomere spacing of 
3·1 µm) and bathed in a K+ solution (K-HDTA) containing (mM): K+, 125; Na+, 37; hexamethylene-diamine-tetraacetate (HDTA2-), 50; total ATP, 8; total magnesium, 8·6; free Mg2+, 1; creatine phosphate, 10; total EGTA, 0·05; Hepes, 90; NaN3, 1; dithiothreitol, 1; pH 7·10 ± 0·01 and pCa (-log10 [Ca2+]) 7·0-7·1. The T-system of a skinned fibre could be depolarised by substituting a similar solution in which all K+ was replaced with Na+. Maximum Ca2+-activated force was determined with a 50 mM Ca-EGTA solution (20 µM free Ca2+) (Lamb & Stephenson, 1990). Electrical field stimulation was applied via two platinum wire electrodes 4 mm apart, running parallel to the skinned fibre segment which was immersed in a 200 µl bath containing K-HDTA solution. Force responses were recorded on a Linear chart recorder and in later experiments were also recorded simultaneously on a Hameg digital storage oscilloscope. Spontaneous contraction waves in skinned fibre segments 3-4 mm long were observed under a Zeiss dissecting microscope (×50 magnification) and recorded with a Sony CCD video camera; records on videotape (frame rate, 25 Hz) were subsequently analysed frame by frame to estimate the propagation velocity of the contraction waves. All experiments were performed at 27 ± 2°C.
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RESULTS |
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Twitch and tetanic responses in mechanically skinned fibres
The surface membrane or sarcolemma of a skeletal muscle fibre can be physically removed with forceps (see Fig. 1A) and the transverse tubular (T-) system seals off to form an isolated compartment (Lamb et al. 1995). When the skinned fibre segment is bathed in a solution that mimics the cytoplasmic environment (high [K+]), a normal membrane potential is evidently established across the T-system membrane, and this can be rapidly dissipated by replacing the K+ in the bathing solution with a less permeant cation (e.g. Na+; Fig. 1C) eliciting Ca2+ release and a force response that peaks after 500 ms (Stephenson, 1985; Fill & Best, 1988; Lamb & Stephenson, 1990, 1994). We now show (Fig. 1B) that transverse electrical field stimulation of a skinned EDL fibre elicited twitch and tetanic responses similar to those occurring in intact fibres. A single 2 ms stimulus (50 V cm-1) evoked a transient force response, peaking within 40 ms at more than 50 % of the maximum force that could be developed in that fibre (Fig. 1C). Repeated stimulation of the same fibre at 11 Hz and at 50 Hz produced unfused and fused tetani, respectively (tetanic stimulation applied for 250-500 ms at intervals > 30 s). Similar results were obtained in each rat EDL fibre examined. Mean peak twitch and 50 Hz tetanic force responses were 36 ± 4 % (± S.E.M.) and 83 ± 4 % of maximum Ca2+-activated force, respectively (n = 23). The response to depolarisation by Na+ substitution in the same fibres (e.g. Fig. 1C) was 89 ± 3 % (n = 22) of maximum Ca2+-activated force. In the nine EDL fibres in which measurements were made at a sufficiently high time resolution, the twitch response had a mean time to peak of 36 ± 2 ms and a half-width of 85 ± 8 ms.
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A, schematic representation of the skinning of a single muscle fibre by rolling back the surface membrane (sarcolemma) with a pair of forceps, forming a 'cuff'. The transverse tubular system (T) seals off to form a closed compartment after skinning. S, sarcolemma; SR, sarcoplasmic reticulum; Z, Z-line; C, contractile apparatus; F, forceps. B, a skinned segment of a rat EDL muscle fibre was mounted on a force transducer and bathed in a solution mimicking the normal cytoplasmic environment (high [K+]), re-establishing the normal resting membrane potential in the sealed T-system. From top to bottom: a single twitch, an unfused tetanus and a fused tetanus (50 Hz) elicited by applying 50 V cm-1 field stimulation (2 ms duration) between two platinum wire electrodes running parallel to the long axis of the fibre. Individual arrows indicate single stimuli and the filled bar indicates a continuous 50 Hz stimulus. C, force response in the same skinned segment elicited when the sealed T-system was depolarised by replacing the K+-based bathing solution with a Na+-based solution, and assessment of maximum force by direct activation of the contractile apparatus with a heavily buffered solution with 20 µM free Ca2+ (Max Act). Fibre segment length (L), 1·2 mm; diameter (D), 50 µm. | ||
For a number of reasons, it was apparent that the responses to electrical stimulation were caused by the generation of action potentials in the sealed T-tubular network. First, if the T-system was kept chronically depolarised by bathing the skinned fibre in a Na+ (zero K+) solution, no response at all could be elicited by field stimulation (up to 90 V cm-1 and 100 Hz) in any of the six rat EDL fibres examined (e.g. Fig. 2A), even though Ca2+ release from the SR could still be triggered directly by applying caffeine (not shown). These results show that electrical field stimulation triggers Ca2+ release by voltage-dependent processes in the T-system that become inactivated with prolonged depolarisation (e.g. voltage-dependent Na+ channels underlying action potential generation and the voltage-sensors in the T-system that control Ca2+ release from the SR; Hodgkin & Horowicz, 1960; Chandler et al. 1976; Hille, 1984; Melzer et al. 1995). Second, the field strength required to elicit a twitch response typically showed a sharp threshold (mean threshold: 19 ± 2 V cm-1 in 7 EDL fibres) with the transition from zero force to > 70 % of maximum twitch size occurring with only an 10 % increase in applied field in the majority of fibres (e.g. Fig. 2B). This property is indicative of an active process such as action potential generation. (It is likely that the response did not show total 'all-or-none behaviour' simply because the T-system in different regions along the fibre had slightly different thresholds to transverse field stimulation.) Third, the presence of 10 µM TTX in the T-tubular network prevented initiation of a twitch response. In these experiments, pairs of whole EDL muscles were bathed in normal extracellular saline solution with or without TTX, and skinned fibres were obtained from each muscle alternately. Skinned fibres not exposed to TTX invariably responded normally to electrical stimulation (twitch response: 28 ± 3 % of maximum force; n = 11), whereas skinned fibres with TTX trapped in the T-system (n = 11) gave no response at all to a single electric pulse (e.g. Fig. 2C), except for two fibres with twitch responses of 5 and 10 % of maximum force, which were presumably cases in which there was incomplete diffusion of TTX into the T-system network. In each case a large response (> 50 % of maximum force) could be elicited by depolarising the T-system by Na+ substitution (e.g. Fig. 2C), showing that the voltage sensors in the T-system were entirely functional and that TTX must have specifically interfered with the ability of the electrical stimulus to trigger full depolarisation of the T-system. When twitch responses were blocked by inclusion of TTX in the T-system, field stimulation at high frequency (50 Hz, 2-4 ms duration) elicited small force responses that were graded with field intensity (Fig. 2C), most probably indicating that the T-system was depolarised sufficiently to directly activate a proportion of the voltage sensors even in the absence of any propagated action potential. To obtain even such small responses by direct activation of the voltage sensors must have required depolarisation to potentials more positive than -60 mV (see Dulhunty, 1992; Posterino & Lamb, 1998), and this is entirely consistent with the field stimulation being able to trigger an action potential when TTX is absent (Pappone, 1980).
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A, twitch responses to field stimulation were abolished when the T-system was chronically depolarised by bathing the EDL fibre in a Na+-based solution (i.e. no K+). Bathing the fibre in a K+-based solution re-established a normal resting membrane potential and restored the ability to evoke a twitch response. Arrows indicate the time of stimulation (60 V cm-1, 2 ms). L, 1·5 mm; D, 40 µm. B, relationship between twitch force and electrical field strength in four EDL fibres (2 ms stimuli). Responses are expressed relative to the maximum twitch size in each fibre. C, responses in a skinned EDL fibre with TTX in the sealed T-system (muscle pre-exposed to 10 µM TTX for 30 min before skinning the fibre). Electrical field stimulation with single 2 ms pulses (60-90 V cm-1) failed to elicit any twitch response, and high frequency stimulation (50 Hz) elicited only a very small force response. In contrast, depolarising the T-system by ionic substitution (Na+ substitution) elicited a large transient force response. Maximum Ca2+-activated force (Max Act) was determined as in Fig. 1. L, 1·5 mm; D, 45 µm. | ||
Propagating spontaneous contractions
In almost all of the skinned EDL fibres examined, particularly at temperatures > 26°C, spontaneous contractions were observed. Such responses occurred either sporadically or in bursts as frequent as once per 5-10 s, and ranged in size from < 5 to 100 % of maximum Ca2+-activated force even in the same fibre (e.g. Fig. 3A). These spontaneous responses were completely blocked in every case by chronic depolarisation of the T-system (Na+ substitution) and were never present in skinned fibres with TTX in the T-system (0/11 fibres), indicating that they were mediated by action potential propagation within the fibre. Spontaneous responses reaching close to maximum force could only have resulted from simultaneous contraction of most of the length of the skinned fibre segment (2·0 mm). As the spontaneous force responses typically reached a peak within 200 ms (mean, 190 ± 40 ms; n = 4; e.g. Fig. 3A), this means that an action potential must have passed internally along the length of the fibre coordinating the activity with an effective longitudinal velocity of greater than 10 mm s-1. These spontaneous contractions could also be observed under the microscope when the skinned fibre segments were left to freely contract in the dish; video recording revealed that waves of contractions started at one or two particular points in a given fibre and spread longitudinally to cause coordinated contraction of regions of 1-2 mm or more in length within 80-120 ms, which again indicated an effective longitudinal conduction velocity of 10-20 mm s-1 (mean, 13 ± 3 mm s-1; n = 7).
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A, spontaneous force responses (*13 % and **91 % of the maximum Ca2+-activated force (Max Act)) recorded in a skinned EDL fibre. Most of the length of the fibre (2·0 mm) must have been simultaneously activated in order to elicit near-maximal force, and even the small spontaneous response must have involved coordinated activation of many sarcomeres. The rise time of the larger spontaneous response (~200 ms) shows that the contraction was synchronised by one or more action potentials travelling along the fibre at an effective longitudinal velocity of ~10 mm s-1. Transverse field stimulation (arrow) evoked a twitch response with a rise time of ~40 ms. Maximum force (Max Act) was determined as in Fig. 1. Segment diameter, 38 µm. B, schematic diagram of the transverse tubular system (T) and the associated longitudinal tubular system (LTS), based on electron micrographs of fast-twitch mammalian fibres in Franzini-Armstrong et al. (1988). The LTS evidently provides a pathway for action potentials (AP) to travel lengthways inside a fibre, ensuring synchronous activation of adjacent sarcomeres even if the action potential on the sarcolemma fails to penetrate the T-system. | ||
The conduit for such action potential propagation must be the longitudinal tubular system (LTS), which electron microscopy (EM) studies (Peachey, 1965; Franzini-Armstrong et al. 1988) have shown links the T-systems of adjacent sarcomeres (see Fig. 3B); such connections can also be visualised by confocal microscopy with a fluophore in the T-system (Stephenson & Lamb, 1992). Further evidence that the T-system was connected longitudinally over many hundreds of sarcomeres was obtained by skinning fibres for only part of their length (e.g. Fig. 1A). Such partially skinned segments were bathed in the standard intracellular K+ solution with 60 µM TTX for 12 min, and then readjusted so that only the fully skinned segment was mounted on the transducer apparatus (see Methods). The TTX could only have entered the T-system of sarcomeres in the skinned segment by passing longitudinally inside the fibre over > 1 mm, from the T-system of sarcomeres in the unskinned region which were open to the external solution. TTX only blocks Na+ channels from within the T-tubules (Hille, 1984), and bath application of TTX (60 µM) to fully skinned fibres had no effect whatsoever on the response to electrical field stimulation. Of the fibres exposed to TTX when partially skinned, almost half (7/15) subsequently failed to give any twitch response to field stimulation (mean twitch in 8 other fibres exposed to TTX: 31 ± 7 % of maximum force), whereas each control fibre (15/15, obtained alternately and treated identically except for the exposure to TTX) gave substantial twitch responses (mean size, 26 ± 4 % of maximum force). This difference is highly significant (P < 0·001, Fisher's exact test) and shows that TTX must have penetrated over long distances along the LTS in many cases, confirming that there is continuity between the tubular networks of adjacent sarcomeres.
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DISCUSSION |
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Response of skinned fibres to electrical stimulation
Transverse electrical field stimulation elicited twitch and tetanic responses in skinned EDL fibres (Fig. 1B) that were very similar to those in intact fibres (e.g. Fryer & Neering, 1988; twitch time to peak 40 ms in small bundles of rat EDL fibres at 25°C). The only appreciable differences in the twitch responses in skinned and intact EDL fibres were that the decay rate of the force response was slightly slower in the skinned fibres and the ratio of twitch to tetanic force exceeded 0·5 in some cases (e.g. Fig. 1B) (cf. Dulhunty, 1992). Both these small differences are expected consequences of the low level of Ca2+ buffering present in the bathing solution (and hence in the cytoplasmic space) in these skinned fibre experiments (50 µM EGTA). Intact EDL fibres contain appreciable amounts of parvalbumin (Rall, 1996), which accelerates the removal of Ca2+ from troponin C by reducing the cytoplasmic [Ca2+]. A further apparent difference was that the tetanic force response to high frequency stimulation declined or 'faded' more quickly (e.g. Fig. 1B) than in intact fibres (Allen et al. 1995). This difference was probably primarily caused by progressive depolarisation of the sealed T-system due to the build-up of K+ during the high frequency stimulation, but a continuous small loss of cytoplasmic Ca2+ from the skinned fibre during the sustained response may have exacerbated the effect.
It is nevertheless clear that the normal E-C coupling process is retained and functional in the skinned fibres, despite the complete absence of any surface membrane. It is also apparent that the twitch responses to electrical stimulation in the skinned fibres must have been elicited by action potentials in the sealed T-system network, because they were abolished by sustained depolarisation of the T-system (Fig. 2A), were steeply dependent on the applied electric field (Fig. 2B), and were prevented by the presence of TTX inside the T-system (Fig. 2C). This demonstrates that normal E-C coupling in mammalian muscle involves propagation of action potentials down the T-system.
Previous attempts to use electrical stimulation to elicit responses in skinned muscle fibres involved application of the electric field along the length of the fibre segment whilst the fibre was kept under paraffin oil (Constantin & Podolsky, 1967; Natori, 1972). Constantin & Podolsky (1967) had to apply current pulses to frog fibres for 200-1000 ms (cf. 2 ms here) to elicit contractions, and these were usually confined to two to five adjacent sarcomeres. Natori (1972) had to apply a field of > 110 V cm-1 for 5 ms to elicit contraction over a region of 50 µm, with the contraction then propagating along the fibre at 2-3 mm s-1 (at 18°C). It is likely that it was easier to evoke large twitch and tetanic responses in the present experiments because (a) the T-system of the fibres was well polarised with the K+ bathing solution used (see Posterino & Lamb, 1998), and (b) the use of transverse field stimulation resulted in a similar level of T-system depolarisation being simultaneously applied to sarcomeres all along the fibre segment, leading to a coordinated contraction.
Spontaneous contractions
Spontaneous contractions were observed to propagate along skinned EDL fibres at 10-20 mm s-1. These contractions were blocked by both chronic depolarisation and the presence of TTX in the T-system, showing that they were triggered by the longitudinal spread of action potentials. Such waves of contractions observed in earlier studies were thought to arise somehow from the spread of excitation through the SR (Constantin & Podolsky, 1967; Natori, 1972). The experiments here in which TTX was evidently able to diffuse down the T-system from an intact region of fibre into the skinned region to block evoked contractions there, show that there is physical and functional continuity of the tubular network lengthways along the fibre via the LTS (Franzini-Armstrong et al. 1988). Although the LTS is relatively sparsely present, we calculate from EM measurements (Franzini-Armstrong et al. 1988) that in the rat skinned fibres studied here (40 µm diameter) there are 60 longitudinal connections between the T-system networks of each adjacent sarcomere. The actual conduction velocity of action potentials in the LTS was probably considerably greater than the speed at which contraction spread along the skinned fibres (i.e. 13 mm s-1), given the rather tortuous pathways involved (Fig. 3B). The fact that spontaneous force responses could be even larger than single twitch responses (e.g. Fig. 3A) could be the result of two or more action potentials being generated in close succession at some site in the T-system (perhaps near the mouth of a poorly sealed T-tubule) or may arise from an action potential 'reverberating' around the tubular network because the initial activation (and concomitant inactivation) of the Na+ channels was not synchronised throughout the fibre.
In intact muscle fibres, propagation of action potentials internally along the LTS would ensure that each sarcomere along the fibre was synchronously activated, as is required for efficient force production. Such internal longitudinal action potential propagation would not replace, but instead complement, the much faster propagation of action potentials along the surface of the fibre; even travelling at only 10 mm s-1 such longitudinal propagation radiating out from the T-system of one sarcomere would activate the three adjacent sarcomeres on either side within 1 ms. This would be particularly important during sustained or repeated muscle contraction, where signal transmission down the T-system from the fibre surface can be hindered by the build-up of K+ and fibre swelling (Fitts, 1994; Allen et al. 1995) and vacuolation of the T-system (Gonzalez-Serratos et al. 1978; Lännergren et al. 1999). Finally, the existence of action potential propagation along the LTS readily explains why the tubular system in developing muscle first forms longitudinally, only making transverse connections at a late stage (Franzini-Armstrong & Jorgenson, 1994); such an arrangement enables entire sections of muscle to contract in synchrony, avoiding damage that would probably otherwise occur if individual sarcomeres were to contract before the network of neighbouring sarcomeres was fully developed.
In conclusion, this study shows (a) that the normal E-C coupling mechanism in skeletal muscle is retained in mechanically skinned fibre preparations and must not require any freely diffusible cytoplasmic factors other than those present in the standard K-HDTA solution (e.g. Mg2+ and ATP), (b) that depolarisation of the T-system in mammalian skeletal muscle is normally mediated by action potentials, and (c) that action potentials are capable of travelling longitudinally inside muscle fibres by an interconnected network of tubules.
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REFERENCES |
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| Allen, D. A., Lännergren, J. & Westerblad, H. (1995). Muscle cell function during prolonged activity: cellular mechanisms of fatigue. Experimental Physiology 80, 497-527 | [Medline] |
| Bezanilla, F., Caputo, C., Gonzalez-Serratos, H. & Venosa, R. A. (1972). Sodium dependence of the inward spread of activation in isolated twitch muscle fibres of the frog. The Journal of Physiology 223, 507-523 | [Medline] |
| Chandler, W. K., Rakowski, R. F. & Schneider, M. F. (1976). Effects of glycerol treatment and maintained depolarization on charge movement in skeletal muscle. The Journal of Physiology 254, 285-316 | [Abstract] |
| Costantin, L. L. (1970). The role of sodium current in the radial spread of contraction in frog muscle fibres. Journal of General Physiology 55, 703-715 | [Medline] |
| Costantin, L. L. & Podolsky, R. J. (1967). Depolarization of the internal membrane system in the activation of frog skeletal muscle. Journal of General Physiology 50, 1101-1124 | [Medline] |
| Dulhunty, A. F. (1992). The voltage-activation of contraction in skeletal muscle. Progress in Biophysics and Molecular Biology 57, 181-223 | [Medline] |
| Fill, M. D. & Best, P. M. (1988). Contractile activation and recovery in skinned frog muscle stimulated by ionic substitution. American Journal of Physiology 254, C107-144 | [Medline] |
| Fitts, R. H. (1994). Cellular mechanisms of muscle fatigue. Physiological Reviews 74, 49-94 | [Medline] |
| Franzini-Armstrong, C., Ferguson, D. G. & Champ, C. (1988). Discrimination between fast- and slow-twitch fibres of guinea pig skeletal muscle using the relative surface density of junctional transverse tubule membrane. Journal of Muscle Research and Cell Motility 9, 403-414 | [Medline] |
| Franzini-Armstrong, C. & Jorgenson, A. O. (1994). Structure and development of E-C coupling units in skeletal muscle. Annual Review of Physiology 56, 509-534 | [Medline] |
| Fryer, M. F. & Neering, I. R. (1988). Actions of caffeine on fast- and slow-twitch muscles of the rat. The Journal of Physiology 416, 435-454. | [Abstract] |
| Gonzalez-Serratos, H., Somlyo, A. V., McClellan, G., Shuman, H., Borrero, L. M. & Somlyo, A. P. (1978). Composition of vacuoles and sarcoplasmic reticulum in fatigued muscle: electron probe analysis. Proceedings of the National Academy of Sciences of the USA 75, 1329-1333 | [Medline] |
| Hille, B. (1984). Ionic Channels in Excitable Membranes. Sinauer Associates, Sunderland, MA, USA. | |
| Hodgkin, A. L. & Horowicz, P. (1960). Potassium contractures in single muscle fibres. The Journal of Physiology 153, 386-403. | |
| Horowicz, P. & Spalding, B. C. (1994). Electrical and ionic properties of the muscle cell membrane. In Myology Basic and Clinical, chap. 14B, ed. Engels, A. G. & Franzini-Armstrong, C., pp. 405-422. McGraw-Hill, New York. | |
| Huxley, A. F. & Taylor, R. E. (1958). Local activation of striated muscle fibres. The Journal of Physiology 144, 426-441. | |
| Lamb, G. D., Junankar, P. R. & Stephenson, D. G. (1995). Raised intracellular [Ca2+] abolishes excitation-contraction coupling in skeletal muscle fibres of rat and toad. The Journal of Physiology 489, 349-362 | [Abstract] |
| Lamb, G. D. & Stephenson, D. G. (1990). Calcium release in skinned muscle fibres of the toad by transverse tubule depolarization or by direct stimulation. The Journal of Physiology 423, 495-517 | [Abstract] |
| Lamb, G. D. & Stephenson, D. G. (1994). Effects of intracellular pH and [Mg2+] on excitation-contraction coupling in skeletal muscle fibres of the rat. The Journal of Physiology 478, 331-339 | [Abstract] |
| Lännergren, J., Bruton, J. D. & Westerblad, H. (1999). Vacuole formation in fatigued single muscle fibres from frog and mouse. Journal of Muscle Research and Cell Motility 20, 19-32 | [Medline] |
| Lüttgau, H. Ch. & Stephenson, D. G. (1986). Ion movements in skeletal muscle in relation to the activation of contraction. In Physiology of Membrane Disorders, chap. 28, ed. Andreoli, T. E., Hoffman, J. F., Fanestil, D. D. & Schultz, S. G., pp. 449-468. Plenum Press, New York. | |
| Melzer, W., Herrmann-Frank, A. & Lüttgau, H. Ch. (1995). The role of Ca2+ ions in excitation-contraction coupling of skeletal muscle fibres. Biochimica et Biophysica Acta 1241, 59-116 | [Medline] |
| Nakajima, S. & Gilai, A. (1980). Radial propagation of muscle action potentials along the tubular system examined by potential-sensitive dyes. Journal of General Physiology 76, 751-762 | [Medline] |
| Natori, R. (1972). Some physiological aspects of internal membrane of skeletal muscle fibers. Jikeikai Medical Journal 19, 51-64. | |
| Pappone, P. A. (1980). Voltage-clamp experiments in normal and denervated mammalian skeletal muscle fibres. The Journal of Physiology 306, 377-410 | [Abstract] |
| Peachey, L. D. (1965). The sarcoplasmic reticulum and the transverse tubules of the frog's sartorius. Journal of Cell Biology 25, 209-231 | [Medline] |
| Posterino, G. S. & Lamb, G. D. (1998). Effects of nifedipine on depolarization-induced force responses in skinned skeletal muscle fibres of rat and toad. Journal of Muscle Research and Cell Motility 19, 53-65 | [Medline] |
| Rall, J. (1996). The role of parvalbumin in skeletal muscle relaxation. News in Physiological Sciences 11, 249-255. | |
| Stephenson, D. G. & Lamb, G. D. (1992). Confocal imaging of key intracellular compartments in muscle fibres. Australian Physiological and Pharmacological Society 23, 244P. | |
| Stephenson, E. W. (1985). Excitation of skinned muscle fibres by imposed ion gradients: I. Stimulation of 45Ca2+ efflux at constant [K][Cl] product. Journal of General Physiology 86, 813-832 | [Abstract] |
This work was supported by the National Health and Medical Research Council of Australia (991496).
Corresponding author
G. D. Lamb: Department of Zoology, La Trobe University, Bundoora, Victoria 3083, Australia.
Email: zoogl{at}zoo.latrobe.edu.au
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 B. S. Launikonis, J. Zhou, L. Royer, T. R. Shannon, G. Brum, and E. Rios Depletion "skraps" and dynamic buffering inside the cellular calcium store PNAS, February 21, 2006; 103(8): 2982 - 2987. [Abstract] [Full Text] [PDF]
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T. L. Dutka, L. Cole, and G. D. Lamb Calcium phosphate precipitation in the sarcoplasmic reticulum reduces action potential-mediated Ca2+ release in mammalian skeletal muscle Am J Physiol Cell Physiol, December 1, 2005; 289(6): C1502 - C1512. [Abstract] [Full Text] [PDF]
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T. L Dutka and G. D Lamb Effect of low cytoplasmic [ATP] on excitation-contraction coupling in fast-twitch muscle fibres of the rat J. Physiol., October 15, 2004; 560(2): 451 - 468. [Abstract] [Full Text] [PDF]
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W. A. Macdonald and D. G. Stephenson Effects of ADP on action potential-induced force responses in mechanically skinned rat fast-twitch fibres J. Physiol., September 1, 2004; 559(2): 433 - 447. [Abstract] [Full Text] [PDF]
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 T. H. Pedersen, O. B. Nielsen, G. D. Lamb, and D. G. Stephenson Intracellular Acidosis Enhances the Excitability of Working Muscle Science, August 20, 2004; 305(5687): 1144 - 1147. [Abstract] [Full Text] [PDF]
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O. B. Nielsen, N. Ortenblad, G. D. Lamb, and D. G. Stephenson Excitability of the T-tubular system in rat skeletal muscle: roles of K+ and Na+ gradients and Na+-K+ pump activity J. Physiol., May 15, 2004; 557(1): 133 - 146. [Abstract] [Full Text] [PDF]
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 B. S. Launikonis and D. G. Stephenson Osmotic Properties of the Sealed Tubular System of Toad and Rat Skeletal Muscle J. Gen. Physiol., February 23, 2004; 123(3): 231 - 247. [Abstract] [Full Text] [PDF]
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T. CLAUSEN Na+-K+ Pump Regulation and Skeletal Muscle Contractility Physiol Rev, October 1, 2003; 83(4): 1269 - 1324. [Abstract] [Full Text] [PDF]
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D. R. Plant and G. S. Lynch Depolarization-induced contraction and SR function in mechanically skinned muscle fibers from dystrophic mdx mice Am J Physiol Cell Physiol, September 1, 2003; 285(3): C522 - C528. [Abstract] [Full Text] [PDF]
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C. Goodman, M. Patterson, and G. Stephenson MHC-based fiber type and E-C coupling characteristics in mechanically skinned muscle fibers of the rat Am J Physiol Cell Physiol, June 1, 2003; 284(6): C1448 - C1459. [Abstract] [Full Text] [PDF]
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G. D. Lamb, G. S. Posterino, T. Yamamoto, and N. Ikemoto Effects of a domain peptide of the ryanodine receptor on Ca2+ release in skinned skeletal muscle fibers Am J Physiol Cell Physiol, July 1, 2001; 281(1): C207 - C214. [Abstract] [Full Text] [PDF]
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